Transverse aortic constriction induces gut barrier alterations, microbiota remodeling and systemic inflammation

Abstract

Accumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.

Qiliqiangxin Modulates the Gut Microbiota and NLRP3 Inflammasome to Protect Against Ventricular Remodeling in Heart Failure

“…Male SD rats (220–250 g), purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. [Animal license number: SCXK (Beijing) 2017–0302], were fed adaptively for 3 days. A model of HF was established surgically through transverse aortic constriction (TAC) operation as has been described ( Ruppert et al, 2020 ), which is one of the most widespread preclinical models of cardiac hypertrophy and HF induced by pressure overload ( Boccella et al, 2021 ). Following anesthesia with sodium pentobarbital (40 mg/kg) and subsequently a left anterolateral thoracotomy, the aortic arch between the brachiocephalic trunk and the left common carotid artery was exposed and then constricted to the size of a 21-gauge needle.…”

“…New therapeutic strategies are needed to be introduced clinically for protecting against pressure overload-induced cardiac injury ( Li X. et al, 2021 ) or targeting adverse post-MI left ventricle remodeling ( Germano et al, 2020 ). Researchers highlight the potential of intestinal microbiota and NLRP3 inflammasomes to impact ventricular remodeling, which hold promise as effective targets for improving cardiac functions in HF ( Boccella et al, 2021 ; Zhao et al, 2021 ). The beneficial effects of QL on cardiac hypertrophy, ventricular remodeling, and HF through multiple pathways have been widely reported ( Gao et al, 2018 ; Lu et al, 2020 ; Wang et al, 2017 ).…”

“…A growing body of evidence derived from the epidemiological and animal model studies uncovers that altered gut microbiota and gut functions are closely related to the development of adverse cardiac remodeling and HF ( Boccella et al, 2021 ; Carrillo-Salinas et al, 2020 ). In chronic heart failure patients, the wall thickness and permeability of the intestine increase, the bacterial populations adhering to the intestinal mucosa release, and bacteria or their toxins transfer from the intestine to the blood directly, which associate with systemic inflammation ( Wang et al, 2021 ).…”

Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

“…Gut microbiota and their metabolites produced from dietary metabolism have been linked to HF. To this extent, gut dysbiosis with decreased microbial richness and increased gut permeability has been reported in patients with HF (57,58), as well as in mice with pressure overload-induced HF (59).…”

“…Gut microbiota and their metabolites produced from dietary metabolism have been linked to HF. To this extent, gut dysbiosis with decreased microbial richness and increased gut permeability has been reported in patients with HF ( 57 , 58 ), as well as in mice with pressure overload-induced HF ( 59 ). Further studies in humans have shown that the gut microbiome-derived metabolite TMAO is increased in HF and that its levels are associated with poor prognosis ( 60 – 64 ).…”